Field of the Invention
Description
Description of Related Art
The invention relates to an improved process for preparing 4-[[(benzoyl)amino]-sulphonyl]benzoyl chlorides.
More particularly, the invention relates to an improved process for preparing 4-[[(2-methoxybenzoyl)amino]sulphonyl]benzoyl chloride and to the use thereof for preparing N-[4-(cyclopropylcarbamoyl)phenylsulphonyl]-2-methoxybenzamide.
N-[4-(Cyclopropylcarbamoyl)phenylsulphonyl]-2-methoxybenzamide (N-[4-(cyclo-propylcarbamoyl)phenylsulphonyl]-o-anisamide) is also referred to as cyprosulfamide. Cyprosulfamide is used as a safener in conjunction with a herbicide, or with a plurality of different herbicides. A safener serves to improve the selectivity of the herbicides used with respect to the crop plants of the particular crop being treated. The term “selectivity” refers to the crop plant compatibility of a herbicide.
Document WO 99/16744 discloses acylsulphamoylbenzamide derivatives and the preparation and use thereof as safeners. However, the preparation processes disclosed in WO 99/16744 relate to the laboratory scale and are found to be not particularly suitable for the industrial preparation of the compounds.
A two-stage process which has likewise been developed for use on the industrial scale for preparation of acylsulphamoylbenzamides is known from document WO 2005/000797 A1. Solvents proposed for the performance of the process known from WO 2005/000797 A1, as well as nonpolar silicone oils, are nonpolar and polar organic solvents.
Organic solvents mentioned explicitly are aliphatic and aromatic hydrocarbons, namely alkanes, for example heptane, octane or alkylated benzenes, for example toluene, dimethylbenzene (xylene), trimethylbenzene or paraffin oil. WO2005/000797 A1 also discloses halogenated aliphatic hydrocarbons, for example dichloromethane or halogenated aromatic hydrocarbons, for example chlorobenzene, dichlorobenzene or haloalkylbenzenes, for example benzotrifluoride.
In contrast, carboxylic esters are not mentioned in WO 2005/000797 A1 as suitable solvents and are accordingly not envisaged for performance of the two-stage process. Nor are ketones, acetamides, nitriles or ethers envisaged as solvents for performance of the two-stage process known from WO 2005/000797 A1. On the basis of the synthesis examples disclosed in WO 2005/000797 A1, in which only the two nonpolar organic solvents chlorobenzene and toluene are used, chlorobenzene and toluene should be considered to be preferred solvents according to the teaching of WO 2005/000797 A1.
There are various reasons for the problem of reduced yields, or the problem of varying yields, in the preparation of 4-[[(2-methoxybenzoyl)amino]sulphonyl]benzoyl chloride. Two of the probably particularly significant reasons are elucidated hereinafter.
The first reason relates to the formation of unwanted dimers. Only after intensive analysis of the first synthesis step, which serves for provision of the 4-[[(2-methoxybenzoyl)-amino]sulphonyl]benzoyl chloride precursor required for formation of cyprosulfamide, was it found that the reactants used for synthesis of said precursor, i.e. the ortho-methoxybenzoic acid compounds of the formula (III) and the 4-sulphamoylbenzoic acid compounds of the formula (IV), are not converted fully because of the formation of dimers when the chlorobenzene solvent is used.
The second reason relates to the further problems connected to the dimer formation in the case of use of the 4-[[(2-methoxybenzoyl)amino]sulphonyl]benzoyl chloride prepared in the process known from WO 2005/000797 A1 in the subsequent process step for preparation of the cyprosulfamide safener. Thus, the incomplete conversion of the abovementioned reactants used for synthesis of the precursor in the process step which serves for preparation of cyprosulfamide promotes the formation of unwanted by-products consisting of the active cyprosulfamide ingredient.
A further unwanted by-product probably forms through condensation of cyprosulfamide with 4-sulphamoylbenzoic acid compounds of the formula (IV).
For the synthesis of 4-[[(2-methoxybenzoyl)amino]sulphonyl]benzoyl chloride in chlorobenzene, WO 2005/000797 A1 (example 1) discloses a yield of 93%. No figures are given as to the extent of dimer formation in connection with example 1, although page 6 lines 21 to 22 of the description of WO 2005/000797 A1 makes it clear in general terms that the formation of unwanted dimers is also to be avoided by the process disclosed in WO 2005/000797 A1.
Nevertheless, it has been found in practice that the problem of dimer formation is not in fact avoided to an optimal degree by the processes known from the prior art. For example, even the filtration of the reaction product of the formula (II) was found to be problematic when the known process was employed on the industrial scale. Moreover, the improved process was to feature increased robustness compared to the known processes. The robustness of a process employable on the industrial scale relates, for example, to the filterability of the reaction solution in the case of varying amounts of product, and the requirement that, on completion of the reaction, the yields does not decrease significantly even if stirring of the reaction mixture continues for a prolonged period.
The requirement for continued stirring of a reaction mixture is not essential for the industrial scale implementation of a reaction. For instance, it may be unavoidable in practice for technical reasons alone that a reaction mixture, on completion of the reaction, is stirred for several more hours, for example overnight. In such a case, the robustness of a process is important.